POS1035 LOW RATES OF RADIOGRAPHIC PROGRESSION WITH 2 YEARS OF GUSELKUMAB, A SELECTIVE INHIBITOR OF THE INTERLEUKIN-23p19 SUBUNIT: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS
Authors: P. J. Mease, A. B. Gottlieb, I. Mcinnes, P. Rahman, A. Kollmeier, X. L. Xu, Y. Jiang, S. Sheng, M. Shawi, S. D. Chakravarty, F. Lavie, D. Van der Heijde
Journal: Annals of the Rheumatic Diseases (2022)

Background In the phase 3 DISCOVER-2 (D2) study, guselkumab (GUS) 100 mg every 4/8 weeks (Q4W/Q8W) significantly improved joint and skin symptoms in patients (pts) with active psoriatic arthritis (PsA); GUS-treated pts had smaller mean changes in radiographic progression vs placebo (PBO) at W24. 1 Clinical response rates and favorable safety profile were durable through W100. 2, 3 Objectives To report details of radiographic assessments comprising Reading Session 3 through W100 of D2, including relationships between radiographic changes and measures of clinical outcomes. Methods Biologic-naïve adults with active PsA (≥5 swollen + ≥5 tender joint count; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24, all through W100. Radiographic Reading Session 3 included assessments at W0/24/52/100 (or at discontinuation after W52) from pts ontinuing study treatment at W52; readers were blinded to treatment group and timepoint. Observed mean changes in total PsA-modified van der Heijde-Sharp (vdH-S), joint space narrowing (JSN), and erosion scores were reported. Changes in total vdH-S scores from W0-100 were determined in pts who did and did not achieve clinical response at W100, assessed by ACR20/50/70, low disease activity (LDA) based on Disease Activity in Psoriatic Arthritis score (DAPSA; ≤14) or Psoriatic Arthritis Disease Activity Score (PASDAS; ≤3.2), minimal disease activity (MDA), and normalized Health-Assessment Questionnaire-Disability Index (HAQ-DI) score (&lt;0.5). Results Of 739 randomized pts, 664 had evaluable data from Reading Session 3; 629 had evaluable data from W52-100. Mean total baseline vdH-S scores were: Q4W, 28.0; Q8W, 23.9; PBO→Q4W, 25.6. Mean progression of joint damage from W0-24 was numerically lower in GUS- than PBO-treated pts for erosion, JSN, and total vdH-S scores (Table 1), consistent with the results from Reading Session 1. 1 Mean changes in radiographic scores from W52-100 indicated low rates of radiographic progression across GUS groups. Among GUS-randomized pts, mean changes in vdH-S score from W0-100 were numerically lower for pts achieving clinical response assessed using ACR20/50/70, DAPSA LDA, PASDAS LDA, MDA, and HAQ-DI vs pts not achieving response at W100 (Figure 1). Table 1. Observed erosion, joint space narrowing, and total PsA-modified vdH-S scores through W100 of DISCOVER-2 GUS Q4W GUS Q8W PBO→GUS Q4W Baseline PsA-modified vdH-S score, n 221 228 215 Erosion 14.2 (23.3) 12.0 (21.9) 12.1 (21.9) Joint space narrowing 13.8 (21.8) 11.9 (19.5) 13.5 (21.6) Total 28.0 (43.6) 23.9 (40.4) 25.6 (42.4) Mean (SD) change in PsA-modified vdH-S score W0-24 N=221 W24-52 N=221 W52-100 N=211 W0-24 N=228 W24-52 N=228 W52-100 N=216 W0-24 N=215 W24-52 N=213 W52-100 N=202 Erosion 0.27 (1.91) 0.36 (1.77) 0.45 (2.90) 0.51 (1.96) 0.20 (1.24) 0.26 (1.75) 0.73 (2.20) 0.25 (1.85) 0.09 (1.98) Joint space narrowing 0.21 (1.17) 0.21 (1.11) 0.30 (1.32) 0.17 (0.69) 0.12 (0.66) 0.20 (0.92) 0.39 (1.72) 0.09 (1.11) 0.04 (1.90) Total 0.48 (2.70) 0.57 (2.66) 0.75 (4.02) 0.68 (2.36) 0.31 (1.57) 0.46 (2.42) 1.12 (3.80) 0.34 (2.79) 0.13 (3.74) Data presented as mean (SD). GUS, guselkumab; PBO, placebo; PsA, Psoriatic Arthritis; Q4W, every 4 weeks; Q8W, every 8 weeks; SD, standard deviation; vdH-S, van der Heijde-Sharp; W, week Conclusion In biologic-naïve pts with active PsA enriched for greater risk of radiographic progression, GUS 100 mg (Q4W or Q8W) was associated with low rates of radiographic progression through 2 years. Pts achieving clinical response across several global measures of disease activity or normalized physical function at W100 had lower mean changes in total PsA-modified vdH-S scores compared with nonresponders. References [1]Mease PJ. Lancet . 2020;395:1126-1136 [2]McInnes IB. Arthritis Rheumatol . 2021;73:604-616 [3]McInnes IB. Innovations in Dermatology . Presentation: March 16-20, 2021 Disclosure of Interests Philip J Mease Consultant of: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Alice B Gottlieb Shareholder of: Xbiotech (stock options only), Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharmaceuticals, UCB, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research and Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research and Development, LLC, Yusang Jiang Employee of: Cytel, Inc., Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research and Development, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Global Services, LLC, Soumya D Chakravarty Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, Frederic Lavie Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Global Services, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, Employee of: Director of Imaging and Rheumatology BV